Immunolocalization of Proinflammatory Cytokines in Myometrium, Cervix, and Fetal Membranes During Human Parturition at Term1

Abstract Each of the proinflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF) α has been identified in reproductive tissues during labor. The cellular origin of these cytokines is unclear. The aim of this study was to localize these proinflammatory cytokines in myometrium (upper and lower segment), cervix, and fetal membranes at term. Biopsies were taken from women undergoing cesarean section either before or after the onset of labor. Immunohistochemistry was used to localize each of the cytokines IL-1β, IL-6, IL-8, and TNFα. Leukocytes were localized using an antibody to CD45. In myometrium and cervix, immunostaining for IL-1β was predominantly in leukocytes. In fetal membranes, IL-1β localized to leukocytes and to the stromal cells of the decidua. In myometrium, IL-6, IL-8, and TNFα were restricted to leukocytes, which were present in greater numbers in tissue obtained during labor. In cervix, IL-6, IL-8, and TNFα localized to leukocytes and glandular and surface epithelium. IL-8 also localized to cervical stromal cells. In fetal membranes, IL-6 and TNFα were expressed by decidual stromal cells, infiltrating leukocytes, and extravillous trophoblasts. In membranes, IL-8 localized to leukocytes in the chorion but was not detected in the amnion. In fetal membranes collected at labor, IL-8 was expressed in decidual stromal cells. Infiltrating leukocytes are a major source of cytokines in uterine tissues during labor.

[1]  W Rath,et al.  Expression of cell adhesion molecules by endothelium in the human lower uterine segment during parturition at term. , 1998, American journal of obstetrics and gynecology.

[2]  R. Menon,et al.  Expression of inflammatory cytokines (interleukin-1 beta and interleukin-6) in amniochorionic membranes. , 1995, American journal of obstetrics and gynecology.

[3]  S. Brennecke,et al.  Interleukin-8 release from human gestational tissue explants: effects of gestation, labor, and chorioamnionitis. , 1999, Biology of reproduction.

[4]  D. Fischer,et al.  Interleukin‐1beta and Interleukin‐8 Concentrations in the Lower Uterine Segment During Parturition at Term , 1998, Obstetrics and gynecology.

[5]  J. Norman,et al.  Cell Adhesion Molecule Expression in the Cervix and Myometrium During Pregnancy and Parturition , 2001, Obstetrics and gynecology.

[6]  J. Ernest,et al.  Fetal fibronectin, interleukin-6, and C-reactive protein are useful in establishing prognostic subcategories of idiopathic preterm labor. , 1995, American journal of obstetrics and gynecology.

[7]  M. Mitchell,et al.  Cytokine abundance in placental tissues: evidence of inflammatory activation in gestational membranes with term and preterm parturition. , 1999, American journal of obstetrics and gynecology.

[8]  R. Hildenbrand,et al.  Identification of Placental Cytokine‐Producing Cells in Term and Preterm Labor , 1998, Obstetrics and gynecology.

[9]  R. Romero,et al.  Interleukin-1 and tumor necrosis factor stimulate arachidonic acid release and phospholipid metabolism in human myometrial cells. , 1993, American journal of obstetrics and gynecology.

[10]  T. Sato,et al.  Tumor necrosis factor-alpha stimulates the biosynthesis of matrix metalloproteinases and plasminogen activator in cultured human chorionic cells. , 1992, Biology of reproduction.

[11]  L. Vatten,et al.  TNF, IL-1, IL-6, IL-8 and soluble TNF receptors in relation to chorioamnionitis and premature labor , 1998, Journal of perinatal medicine.

[12]  G. Wiedswang,et al.  Tumor necrosis factor, interleukin-1, and interleukin-6 in normal human pregnancy. , 1993, American journal of obstetrics and gynecology.

[13]  A. Steinborn,et al.  Signal for term parturition is of trophoblast and therefore of fetal origin. , 1995, Prostaglandins.

[14]  R. Hildenbrand,et al.  Cytokine release from placental endothelial cells, a process associated with preterm labour in the absence of intrauterine infection. , 1999, Cytokine.

[15]  J. Norman,et al.  Changes in the expression of nitric oxide synthase in the human uterine cervix during pregnancy and parturition. , 2000, Molecular human reproduction.

[16]  A. Malmström,et al.  Interleukin-8 is a mediator of the final cervical ripening in humans. , 1997, European journal of obstetrics, gynecology, and reproductive biology.

[17]  N. Takai,et al.  Interleukin-1beta and interleukin-8 in cervicovaginal fluid during pregnancy. , 1998, American journal of obstetrics and gynecology.

[18]  R. Menon,et al.  Inflammatory cytokine (interleukins 1, 6 and 8 and tumor necrosis factor-alpha) release from cultured human fetal membranes in response to endotoxic lipopolysaccharide mirrors amniotic fluid concentrations. , 1996, American journal of obstetrics and gynecology.

[19]  I. Cameron,et al.  Leukocytes infiltrate the myometrium during human parturition: further evidence that labour is an inflammatory process. , 1999, Human reproduction.

[20]  J. Blaser,et al.  Interleukin‐8 synthesis and the onset of labor , 1995, Obstetrics and gynecology.

[21]  Je‐ho Lee,et al.  Up-regulation of matrix metalloproteinase-9 in human myometrium during labour: a cytokine-mediated process in uterine smooth muscle cells. , 2000, Molecular human reproduction.

[22]  P. Hatthachote,et al.  Complex interactions between sex steroids and cytokines in the human pregnant myometrium: evidence for an autocrine signaling system at term. , 1999, Endocrinology.

[23]  E. Norwitz,et al.  The control of labor. , 1999, The New England journal of medicine.

[24]  A. Malmström,et al.  Human cervical ripening, an inflammatory process mediated by cytokines. , 2000, Molecular human reproduction.

[25]  M. Ståhle-Bäckdahl,et al.  The Human Cationic Antimicrobial Protein (hCAP18), a Peptide Antibiotic, Is Widely Expressed in Human Squamous Epithelia and Colocalizes with Interleukin-6 , 1999, Infection and Immunity.

[26]  M. Sullivan,et al.  Effects of interleukin-6 and tumor necrosis factor-alpha on prostaglandin production by cultured human fetal membranes. , 1993, Prostaglandins.

[27]  H. Zahradnik,et al.  Formation of proinflammatory cytokines in human term myometrium is stimulated by lipopolysaccharide but not by corticotropin-releasing hormone. , 2000, The Journal of clinical endocrinology and metabolism.

[28]  R. Romero,et al.  Cytokine‐Initiated Signal Transduction in Human Myometrial Cells , 1993, American journal of reproductive immunology.

[29]  J. Halgunset,et al.  Cytokine levels in amniotic fluid and inflammatory changes in the placenta from normal deliveries at term. , 1994, European journal of obstetrics, gynecology, and reproductive biology.

[30]  R. Kelly,et al.  Regulation of interleukin 8 production in the term human placenta during labor and by antigestagens. , 1998, American journal of obstetrics and gynecology.

[31]  T. Terao,et al.  Expression of interleukin‐8 receptors in the gestational tissues before and after initiation of labor: Immunohistochemical study , 1996, Acta obstetricia et gynecologica Scandinavica.

[32]  M. Morgan,et al.  Association of polymorphism within the promoter of the tumor necrosis factor alpha gene with increased risk of preterm premature rupture of the fetal membranes. , 1999, American journal of obstetrics and gynecology.